Heck (or Mizoroki-Heck) coupling is a valuable synthetic method for coupling compounds, thereby forming a new carbon-carbon bond between a first compound and a second compound. Traditionally, Heck coupling partners consist of a first compound having a halide or triflate (trifluoromethanesulfonate) substituent and a second compound comprising an alkene.
It is known that triflates, having the formula F3CSO2—, may be used in the place of the halides in Heck couplings, however the expense of triflic anhydride (CF3SO2)2O has limited the use of triflates in Heck couplings to the production of fine chemicals. Further, the atom economy of triflic anhydride is low since half of the molecule is expended as monomeric triflate anion (CF3SO2−) as a result of condensation with a phenolic precursor.
In addition, it is recognized that some compounds having a triflate substituent hydrolyze in the presence of water, and therefore can require anhydrous conditions to achieve high yield and selectivity. In such cases it is further recognized that unless anhydrous conditions are employed, the amount of ligand and catalyst relative to substrate must be high to achieve reasonable yields.
It is also known that aryl methanesulfonates (also known as mesylates) are suitable for Heck couplings, for example aryl-olefin couplings. One drawback of coupling reactions using aryl methanesulfonates is that these reactions require expensive palladium catalysts. When performing a Heck coupling using either a triflate or methanesulfonate, it is common to perform the reaction in two steps, a first step comprising replacing the hydroxyl group on a first compound with the triflate or the methanesulfonate, and a second step comprising coupling the first compound with the second compound. A separation step is generally required between the first and second steps.
It would be desirable to have a replacement for triflates and methanesulfonates which allow Heck coupling reactions. Furthermore, a water-stable triflate replacement could ensure lower loadings of expensive catalysts. In addition, it is desired to have a cross-coupling reaction which has greater atom economy.